0000000000445021
AUTHOR
Gergely Imre
Caspase-2 is an initiator caspase responsible for pore-forming toxin-mediated apoptosis
Bacterial pathogens modulate host cell apoptosis to establish a successful infection. Pore-forming toxins (PFTs) secreted by pathogenic bacteria are major virulence factors and have been shown to induce various forms of cell death in infected cells. Here we demonstrate that the highly conserved caspase-2 is required for PFT-mediated apoptosis. Despite being the second mammalian caspase to be identified, the role of caspase-2 during apoptosis remains enigmatic. We show that caspase-2 functions as an initiator caspase during Staphylococcus aureus alpha-toxin- and Aeromonas aerolysin-mediated apoptosis in epithelial cells. Downregulation of caspase-2 leads to a strong inhibition of PFT-mediate…
The sphingosine kinase 1 activator, K6PC-5, attenuates Ebola virus infection
Summary Ebola virus (EBOV) is responsible for outbreaks with case fatality rates of up to 90% and for an epidemic in West Africa with more than ten thousand deaths. EBOV glycoprotein (EBOV-GP) is the only viral surface protein and is responsible for viral entry into cells. Here, by employing pseudotyped EBOV-GP viral particles, we uncover a critical role for sphingolipids in inhibiting viral entry. Sphingosine kinase 1 (SphK1) catalyzes the phosphorylation of sphingosine to sphingosine 1-phosphate (S1P). The administration of the SphK1 activator, K6PC-5, or S1P, or the overexpression of SphK1 consistently exhibited striking inhibitory effects in EBOV-GP-driven entry in diverse cell lines. F…
The Sphingosine Kinase-1 Activator, K6PC-5, Attenuates the Ebola Virus Infection and the Virus Induced Cell Death
Ebola virus (EBOV) is responsible for outbreaks with case-fatality rates of up to 90% and for an epidemic in West Africa with more than ten thousand deaths. EBOV glycoprotein (EBOV-GP) is the only viral surface protein and is responsible for viral entry into cells. It has been suggested to play a role in the cytopathic effects induced by the virus. Here we uncover a critical role for sphingolipids in inhibiting viral entry and virus-mediated cytotoxicity. Sphingosine kinase 1 (SphK1) catalyzes the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P). The administration of the SphK1 activator, K6PC-5, or S1P, or the overexpression of SphK1 consistently exhibited striking inhibito…